CHCHD4 Regulates Intracellular Oxygenation and Perinuclear Distribution of Mitochondria

Frontiers in Oncology
Luke W ThomasMargaret Ashcroft

Abstract

Hypoxia is a characteristic of the tumor microenvironment and is known to contribute to tumor progression and treatment resistance. Hypoxia-inducible factor (HIF) dimeric transcription factors control the cellular response to reduced oxygenation by regulating the expression of genes involved in metabolic adaptation, cell motility, and survival. Alterations in mitochondrial metabolism are not only a downstream consequence of HIF-signaling but mitochondria reciprocally regulate HIF signaling through multiple means, including oxygen consumption, metabolic intermediates, and reactive oxygen species generation. CHCHD4 is a redox-sensitive mitochondrial protein, which we previously identified and showed to be a novel regulator of HIF and hypoxia responses in tumors. Elevated expression of CHCHD4 in human tumors correlates with the hypoxia gene signature, disease progression, and poor patient survival. Here, we show that either long-term (72 h) exposure to hypoxia (1% O2) or elevated expression of CHCHD4 in tumor cells in normoxia leads to perinuclear accumulation of mitochondria, which is dependent on the expression of HIF-1α. Furthermore, we show that CHCHD4 is required for perinuclear localization of mitochondria and HIF activation...Continue Reading

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Citations

Mar 7, 2020·Biological Chemistry·Yannik Finger, Jan Riemer
Oct 20, 2018·Frontiers in Oncology·Thomas BristonMargaret Ashcroft
Feb 16, 2019·Cellular and Molecular Life Sciences : CMLS·Luke W Thomas, Margaret Ashcroft
Mar 8, 2020·Nature Reviews. Molecular Cell Biology·Pearl LeeM Celeste Simon
Feb 19, 2021·Biochemical Society Transactions·Hasan Al-Habib, Margaret Ashcroft
Feb 28, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Camille ReinhardtNazanine Modjtahedi
Aug 28, 2021·Biology·Laura Lestón PinillaLuigi A De Girolamo

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Methods Mentioned

BETA
Profiler
transfection
PCR
electron microscopy

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